Rapid RBC growth and subsequent multiplex asexual division presents severe metabolic challenges. The parasite has adapted to these challenges by acquiring the ability to rapidly digest millimolar levels of hemoglobin (Hb) acquired from the RBC cytosol. Hb digestion via elegant internalization and proteolysis within a unique lysosomal-like organelle termed the digestive vacuole (DV) is essential for parasite survival. The toxic by product, heme, released upon Hb proteolysis, cannot be degraded by the parasite because it lacks the heme oxygenase pathway. Instead, the parasite is one of only a handful of organisms on the planet that detoxifies copious amounts of heme by crystallization to hemozoin (Hz), as described later. Thus, this pathway is a specific, biochemically unique drug target. Key molecular details of this pathway have been elucidated in recent years. In parallel, drug-resistance researchers are defining how drug-pathway interactions are 'hijacked' by the drug-resistant parasite via subtle alterations in DV bio chemistry and physiology. In a desperate time, some optimism is on the horizon.