Abstract Context Medical therapies derived from natural sources have been used for centuries. Many are as effective as synthetic medications. The use of plant-derived medications for benign prostatic hyperplasia (BPH) is no exception. In particular, extracts of Serenoa repens (SrE), the fruit of the American dwarf palm, are widely available, and their use is rising throughout the world. Objective The underlying basis for SrE popularity stems from its safety and tolerability profile. However, despite its extensive use, its mechanism of action has not been definitely clarified. In this paper, we analyse the scientific basis for SrE efficacy in the treatment of BPH and explore the mechanisms by which its effects are induced. Evidence acquisition This literature review focuses on the actions of the lipidosterolic SrE on a host of targets. Several cellular and molecular techniques have been used to characterise the biologic pathways that may mediate these actions. Morphologic studies have been carried out to identify the changes of prostate ultrastructure and to determine modifications that may shed light on the mechanisms underlying SrE efficacy. Evidence synthesis Selectivity of the action of SrE for the prostate has been demonstrated. There are several morphologic changes, and these are accompanied by an increase in the apoptotic index of the gland, along with inhibition of the activity of the 5α-reductase isoenzymes. The drug also acts on a number of other biologic systems and shows a capacity to moderate the androgenic, apoptotic, and inflammatory pathways of the cell. These pathways have been implicated in the hyperplastic process. Conclusions The interaction between prostate cells and SrE is manifest at several levels of the gland's biological spectrum and results in antiandrogenic, anti-inflammatory, and proapoptotic effects. These effects may account for the beneficial response triggered in some patients with BPH treated with SrE.