Drug-drug interaction is a matter of deep concern as this proves to be the major cause of adverse drug reaction (ADR). It may be on pharmacokinetic or pharmacodynamic level. Pharmacokinetic interactions involve the effect of absorption, distribution, metabolism and excretion whereas pharmacodynamic interactions emphasize mainly on three areas viz.,  interactions that occur at single receptor site, at variety of receptor sites and general non-specific interactions mediated through unspecified sites of action. Different factors are responsible such as genetic constitution, disease, diet, pharmacological response and polypharmacy, age related physiological changes on the basis of the outcomes obtained on the clinical effects of the drug used. This article reflects a clear picture on drug-drug interactions for cytochrome p-450 and non steroidal anti-inflammatory drug (NSAIDs), antihistaminic drugs, antidepressants, interactions with antiretrovirals and Rifampin, anti-anaemic agents, dermatological drugs, antipsychotic drugs, major antibiotics, sedative-hypnotic and anti-cancer drugs.