Atovaquone is a unique naphthoquinone with broad-spectrum antiprotozoal activity. It is effective for the treatment and prevention of Pneumocystis carinii pneumonia (PCP), it is effective in combination with proguanil for the treatment and prevention of malaria, and it is effective in combination with azithromycin for the treatment of babesiosis. There is also limited experience with other protozoans. It has found a role in the management of diseases such as malaria and PCP because drug resistance, intolerable side effects of medications, and variable efficacies have occurred with existing treatments. Although the antimicrobial actions of the naphthoquinones were demonstrated more than 50 years ago, clinical trials leading to Food and Drug Administration (FDA) approval of atovaquone have occurred largely over the last decade. This paper reviews the pharmacology and mechanism of action, clinical trials, and current uses of atovaquone.