Heterocyclic compounds are cornerstone for active pharmaceutical ingredients. Among heterocycles, isoindoline core occupies special place as ten commercial bioactive compounds/drugs contain this skeleton decorated with several functional groups required for optimal receptor binding. These drugs are employed for indications such as multiple myeloma, leukemia, inflammation, hypertension, edema, obesity, and insect control. This review presents pharmacological activities, mechanisms of action and chemical syntheses of these commercial bioactive molecules/drugs.