Protein-energy malnutrition (PEM) is a major public health problem affecting a high proportion of infants and older children world-wide and accounts for a high childhood morbidity and mortality in the developing countries. The epidemiology of PEM has been extensively studied globally and management guidelines formulated by the World Health Organization (WHO). A wide spectrum of infections such as measles, malaria, acute respiratory tract infection, intestinal parasitosis, tuberculosis and HIV/AIDS may complicate PEM with two or more infections co-existing. Thus, numerous drugs may be required to treat the patients. In-spite of abundant literature on the epidemiology and management of PEM, focus on metabolism and therapeutic drug monitoring is lacking. A sound knowledge of pathophysiology of PEM and pharmacology of the drugs frequently used for their treatment is required for safe and rational treatment. In this review, we discuss the pathophysiological changes in children with PEM that may affect the disposition of drugs frequently used for their treatment. This review has established abnormal disposition of drugs in children with PEM that may require dosage modification. However, the relevance of these abnormalities to the clinical management of PEM remains inconclusive. At present, there are no good indications for drug dosage modification in PEM; but for drug safety purposes, further studies are required to accurately determine dosages of drugs frequently used for children with PEM.