Montuschi signiﬁcantly improve symptoms, exercise tolerance and general health status (Cazzola et al 1995; Ulrik 1995; Boyd et al 1997). Both β2-agonists and long-acting anticholinergics reduce the frequency of exacerbations in COPD (Rennard et al 2001; Casaburi et al 2002) although the mechanism(s) of this effect is currently unknown. Possible anti- inﬂammatory effects of long-acting β2-agonists (Johnson and Rennard 2001) might explain the reduced frequency of exacerbations of COPD (Mahler et al 1999; Rennard et al 2001; Calverley, Pauwels, et al 2003). These bronchodi- lators do not seem to cause tachyphylaxis, namely rapid reduction in the intensity of the pharmacological effect due to continued or repeated administration, and are well tolerated. Although bronchodilator treatment in COPD is generally started with a single agent, the use bronchodila- tors in combination is suggested in the current guidelines as this strategy can result in improved bronchodilator and clinical effect (GICOPD 2001; Celli and McNee 2004). However, the interindividual variability of the bronchodilating effect can be high. The efﬁcacy of combin- ing either short or long-acting β2-agonists with anticholin- ergics (COMBIVENT 1994; van Noord et al 2000, 2006), anticholinergics and theophylline (Bleecker and Britt 1991; Bellia et al 2002), and all three classes of bronchodilators is known (Nishimura et al 1995). A ﬁxed inhaled combination of albuterol and ipratropium is available. High doses of nebulized bronchodilators are still widely prescribed for severe COPD. The British Thoracic Society (BTS) guidelines on nebulizer therapy (NPG 1997) recommend that a respiratory physician should evaluate the effectiveness of nebulizer therapy. Before trying chronic nebulizer therapy, it is advisable to evaluate the efﬁcacy of high dose bronchodilator treatment delivered by metered dose inhaler (MDI) with a spacer. The administration of theophylline for stable COPD remains controversial. Theophylline causes bronchodilation in COPD (Murciano et al 1989; McKay et al 1993) with a variable effect on exercise tolerance and symptoms (Murciano et al 1984; Cooper et al 1987; Chrystyn 1988; Mulloy and McNicholas 1993). Theophylline has a slow onset of action and it is generally recommended for maintenance treatment, rather than for the rapid treatment of symptoms. In the major guidelines for the treatment of COPD, theophylline is considered a third line bronchodilator after inhaled anticholinergics and β2 agonists (Barnes 2006). Nevertheless, theophylline is a useful treatment in patients with severe COPD as its withdrawal leads to signiﬁcant clinical worsening of the 416 disease (Kirsten DK 1993). The most recent and largely selective phosphodiesterase inhibitors, such as inhibitors of phosphodiesterase type 4 isoenzyme, slightly improve lung function in COPD (Compton et al 2001) and reduce the frequency of exacerbations (Edelson et al 2001; Rabe et al 2005; Rennard et al 2006) (see below). However, further studies are needed to adequately evaluate the efﬁcacy and tolerability of this new class of drugs. Long-acting bronchodilators administered once or twice daily can improve symptoms to the same extent or more compared with chronic administration of short-acting bron- chodilators. For this reason it is possible to consider the use of long-acting bronchodilators for the treatment of COPD patients requiring chronic treatment to improve symptoms. Theophylline may be recommended for patients with persistent symptoms instead of long-acting bronchodilator treatment. However, because of the disadvantages outlined above, administration of theophylline should be continued only if its efﬁcacy on the symptoms has been demonstrated. The role of theophylline in the treatment of COPD is currently being re-evaluated based on important pharmacological evidence which has allowed the molecular mechanism of action of theophylline to be clariﬁed (Barnes 2003). Inhaled glucocorticoids are generally prescribed for COPD without demonstration of their effectiveness. However, COPD patients generally have no, or a negligible, response to glucocorticoids (Pauwels et al 1999; Vestbo et al 1999; Burge et al 2000; LHSRG 2000; RS 2003). Some patients may improve after glucocorticoid treatment, but it is likely that these patients have concomitant asthma (Barnes 2000). A two-week trial of oral glucocorticoids was proposed to identify patients with a documented spirometric response, assuming that an acute response is predictive of a chronic response (GISCOPD 2001). However, the oral administration of glucocoticoids for two weeks does not generally allow identiﬁcation of those patients who will respond to inhaled glucocorticoids (Senderovitz et al 1999; Burge et al 2000, 2003). Therefore, a trial of glucocorti- coids is not generally recommended for COPD (GISCOPD 2001), unless required to exclude asthma (Barnes 2000). Glucocorticoids do not reduce airway inflammation in COPD (Barnes 2000) and various long-term studies showed that glucocorticoids are not able to reduce the progression of COPD (Pauwels et al 1999; Vestbo et al 1999; Burge et al 2000; LHSRG 2000). For this reason, and taking into account the risk of systemic side effects, particularly at high doses, glucocorticoids should not generally be administered for COPD (Barnes 2000), though they are recommended International Journal of COPD 2006:1(4)