Rapid-cycling bipolar disorder (RCBD) is currently defined as the presence of at least four affective episodes per year. RCBD is often difficult to treat with standard therapies bipolar disorder (BD), thus dictating special treatment strategies. This is especially true for the treatment of RCBD with lithium, which has been described as insufficient to prevent the high-frequency episodes in up to 82% of cases. There are several other possibilities for the biological treatment of RCBD, including the mood-stabilizers carbamazepine (CBZ) and valproate, neuroleptics, antidepressants, calcium channel blockers, l-thyroxine, benzodiazepines. ECT, total sleep deprivation and several other less proven agents. The utility of these agents and treatment procedures in the acute and prophylactic treatment of RCBD is reviewed. Special emphasis is placed on the controversial discussion of the possible induction and worsening of RCBD by antidepressant treatment. Finally, a number of guidelines for the pharmacological management of RCBD are proposed.