with this resistance profile, raltegravir has been the target of an excessive amount of me-too research and development over the last two years. Though, again, there have been historical instances of me-too drugs significantly benefiting patients and instigating medical progress, they have for the most part only benefited pharmaceutical companies. Although it is definitely possible that the next blockbuster anti-HIV drug could be a raltegravir lookalike, we hypothesize that raltegravir me-too drugs, targeting a virus that exhibits an extraordinary rate of resistance evolution, will experience a low probability of success in the clinical setting due to viral resistance and cross-resistance issues. Me-too or second generation? In contrast to me-too drugs, second generation HIV-1 IN inhibitors benefit patients. In order to be considered a bona fide second generation inhibitor, a compound of interest must meet at least one of three criteria (Figure 2 ). First, a second generation inhibitor may exhibit a new mode of action and/or contain novel active substituent(s). A second generation inhibitor may also possess significantly improved potency and/or significantly decreased toxicity. Thirdly, a second generation inhibitor may exhibit potency while avoiding cross-resistance from mutants resistant to similar drugs. Obviously, the more criteria a selected drug meets, the more success it will enjoy in the clinical setting and in the global market. A recent example of a second generation drug that has narrowly avoided me-too labeling is the protease inhibitor, darunavir. Darunavir is the 10 th protease inhibitor to be marketed in the United States, and it was