In various aspects, the invention provides pharmacologic and genomic methods of inhibiting fertility in a male animal, such as human male contraception, involving the manipulation of the activity of hormone-sensitive lipase, including inhibiting the activity of a hormone-sensitive lipase in the animal. In another aspect, the invention discloses the use of hormone-sensitive lipase as a target in screening assays that may be used to identify compounds that modulate male fertility. In another aspect, the present invention identifies a condition of male infertility caused by hormone-sensitive lipase deficiency.