Four types of combination therapy may be used in the treatment of depression: anxiolytics and antidepressants, neuroleptics and antidepressants, co-administration of two or more antidepressants, association of antidepressants with drugs correcting antidepressant-induced side-effects. First, the pros and cons of these combinations are described as they appear in daily practice. In the second part, the theoretical reasons for supporting or contraindicating such combinations are discussed in the light of pharmacological data. The value of recent molecules such as nomifensin, viloxazin, amineptin and mianserin which interact with a minimum number of neurotransmitters is stressed.