During the last two years important advances in the diagnosis and treatment of cytomegalovirus (CMV) disease have occurred. Several studies have suggested that biologic markers of CMV viremia (PCR, branched DNA and pp65 antigenemia) might be useful both to stratify the risk of developing CMV disease and to follow the response of CMV retinitis to therapy. It has been shown that patients who are plasma CMV PCR positive have a risk of developing CMV disease three times higher than patients who are plasma CMV PCR negative. In addition, for each log10 increase of the CMV viral load there is a 3-fold higher risk of developing CMV disease. Currently, therapeutic options for induction treatment of CMV retinitis (CMVR) are: i.v. ganciclovir (GCV), i.v. foscarnet, i.v. cidofovir or GCV intraocular implant combined with oral GCV. For maintenance therapy options are: i.v. GCV (3, 5 or 7 days per week), oral GCV (only for peripheral retinitis), i.v. foscarnet (daily), i.v. cidofovir (biweekly) and GCV intraocular implant (replaced every 6-8 months) combined with oral GCV. There is currently enough evidence to allow the diagnosis of progressive multifocal leukoencephalopathy (PML) based on the finding of JC virus DNA in CSF by PCR. There are still no drugs with proven clinical efficacy against JC virus but the possibility that HAART treatments might improve the control of this disease appear promising.