Splenomegaly results from different abnormal conditions susceptible to drugs. Their diagnosis is based on a history of exposure to a drug before the spleen enlargement. This paper reviews studies on drugs that may induce to splenomegaly. Drugs may provoke the enlargement of the spleen by direct effect on splenic cells or as a side effect of disturbances in other organs, such as the liver, or systems, such as the haematoimmunological system. Some drugs provoke severe haemolysis associated with splenomegaly. Another cause of spleen increasing in size is the venous congestion due to liver disturbance with portal vein occlusion as side complications of drugs. All these drug side effects are usually transitory and splenomegaly disappears when the medication is discontinued. This is a complex problem that must be better studied to be understood in order to prevent its occurrence and to find the best treatment.