BACKGROUND: In contrast to the broad literature on depression in the general population, little is known about the management of depression affecting gay men and HIV-positive men attending general practice clinics. OBJECTIVE: This paper explores qualitative descriptions of how depression in gay men and HIV-positive men is managed by GPs. METHODS: As part of the qualitative component of a mixed method study on HIV and depression, semi-structured interviews were conducted with 16 GPs in three geographical settings in Australia: Sydney, Adelaide and a rural coastal town. RESULTS: GPs identified a range of features in their experience of managing depression in gay men and in HIV-positive men. Some were common to the care of other groups with depression, but this paper reports on features unique to this patient group. These include capitalizing on the high frequency of contact with this patient group, taking advantage of the specialist multidisciplinary teams who provide support, building upon the unusual willingness of this patient group to take medication, appreciating the central importance to many gay men of sexual functioning, and recreational drug use, responding to social isolation in this patient group and coping with increasing challenges for the HIV general practice workforce. CONCLUSIONS: Despite the identification of several key strengths in working with this patient group, the ability of GPs to develop their capacity to manage depression in gay men and men with HIV is uncertain in the context of a growing range of challenges for GPs in both mental health and HIV care.