The human genome encodes 40 voltage-gated K⁺ channels (K_V), which are involved in diverse physiological processes ranging from repolarization of neuronal and cardiac action potentials, to regulating Ca²⁺ signalling and cell volume, to driving cellular proliferation and migration. K_V channels offer tremendous opportunities for the development of new drugs to treat cancer, autoimmune diseases and metabolic, neurological and cardiovascular disorders. This Review discusses pharmacological strategies for targeting K_V channels with venom peptides, antibodies and small molecules, and highlights recent progress in the preclinical and clinical development of drugs targeting the K_V1 subfamily, the K_V7 subfamily (also known as KCNQ), K_V10.1 (also known as EAG1 and KCNH1) and K_V11.1 (also known as HERG and KCNH2) channels.