Paclitaxel has unique activity in angiosarcomas of the face and scalp, but its activity in angiosarcomas originating at other sites is less well defined. Paclitaxel and pegylated-liposomal doxorubicin (PLD) are highly effective in Kaposi sarcoma (KS). Because of the efficacy of PLD in soft tissue sarcoma in general, and in KS in particular, coupled with potential similarities in KS and angiosarcoma, and the apparent activity of paclitaxel in angiosarcomas, the authors treated patients with angiosarcoma with either paclitaxel or PLD as initial chemotherapy. To better define the efficacy of these agents in angiosarcoma, the authors reviewed their experience with paclitaxel and PLD in patients with angiosarcoma treated between 1994 and 2004. They identified seven patients with angiosarcoma treated with paclitaxel, and six treated with PLD. Only one patient in the series had an angiosarcoma of the scalp. Two patients receiving paclitaxel had received previous therapy with PLD, and four of six patients treated with PLD had previously received paclitaxel. Of the eight patients treated with paclitaxel, five had major responses (three had partial responses [PR] and two had complete disease remission [CR]) and three had progressive disease (PD). Of the 6 patients who received PLD, 3 had a PR for 6, 19, and >20 months, respectively, 2 had stable disease for 7 and 11 months, respectively, and 1 had PD. The current study demonstrated the activity of PLD (five of six patients experienced clinical benefit) and extended the data on paclitaxel in angiosarcoma, both of the face and scalp, as well as angiosarcoma originating at other sites.