There is increasing evidence that therapeutic agents for raising HDL would be a useful addition to the current treatment approach for preventing coronary heart disease (CHD), especially considering the fact that therapies for lowering LDLs are not fully adequate for preventing CHD. The recent unraveling of some of the complexities of HDL metabolism has led to the identification of new key proteins involved in HDL metabolism, thus giving new hope and ideas for drug targets. This review focuses on apolipoprotein AI mimetic peptides, which are currently being explored as therapeutic agents for a new treatment strategy known as acute HDL therapy.