The drugs most commonly used for treatment of toxoplasmosis combine folate inhibitors that frequently cause undesirable side effects. There is an urgent need for new drugs or drug combinations that are able to eradicate the tissue cysts responsible for relapses, particularly for patients intolerant to folate inhibitors. Although promising for its activity against cysts, atovaquone is still limited by its variable intestinal absorption. The recent demonstration that the apicoplast of Toxoplasma gondii could be a possible unique drug target for antibiotics such as macrolides and fluoroquinolones represented an important breakthrough in this area.