Severe thrombocytopenia as a complication of CMV infection in immune competent adults is uncommon with only a few cases reported in the literature. The mechanism of CMV-related thrombocytopenia is unclear, resulting in a wide range of treatments used. The use of the antiviral agent ganciclovir was reported in five cases, with variable results. The use of foscarnet, which does not share the myelosuppressive effects of ganciclovir, in adult immune competent patients has not been reported. We review the literature and report two cases of CMV-related thrombocytopenia that were treated with foscarnet. In both cases a recent acute infection with CMV was well established and viral eradication following treatment with foscarnet was demonstrated. In one patient thrombocytopenia resolved following treatment with foscarnet and viral eradication. In the other patient, thrombocytopenia resolved following splenectomy, which was performed after viral eradication. Due to the therapeutic consequences of this diagnosis, it may be worthwhile to perform CMV screening in selected patients with thrombocytopenia. In case CMV viremia is demonstrated, viral eradication seems to have a positive influence on the resolution of thrombocytopenia. Foscarnet is a reasonable first line anti CMV agent in this setting.