Important obstacles facing programs involved in eradication of tropical diseases are drug resistance and environmental aspects surrounding the infected population including poverty, inefficient healthy sewage system, and popular habits. Treatment failure is determined by either persistence of clinical manifestations after scheduled drug regimen, or occurrence of disease relapse or new infections. This means that treatment failure in clinical studies does not mean drug resistance because identified parasite' resistance to a certain drug does not include pharmacokinetics and pharmacogenetics studies as well as host immunological assessment. Coinfections, drug-drug interactions, and environmental factors also contribute in development of drug resistance. Of note, parasite gene mutation is the main mechanism suggested for drug resistance. The present work aims to review commonly reported drugs associated with resistance, and the proposed genetic markers of resistance