There are four classes of antiretroviral agents used in the treatment of HIV/ AIDS. Adverse effects to Highly Active Antiretroviral Therapy (HAART) are common and often difficult to avoid. In many cases, research is not able to identify the exact cause of an adverse event. The severity of adverse reactions varies greatly and difficult to manage; typically prevention is more desirable than treatment. However, this is not always true. This paper will review safety aspect of class-wide Highly Active Antiret-roviral Therapy, mechanism of action. A class-wide adverse effect for Reverse tran-scriptase inhibitors includes lactic acidosis, peripheral neuropathy and lipoatrophy. Class wide adverse effects to non-nucleoside reverse transcriptase inhibitors include rash and hepatotoxicity, while efavirenz has its own unique CNS reactions. Protease inhibitor side effects include hyperglycemia, lipoaccumulation, dyslipidemia, and gastrointestinal (GI) intolerance. Coreceptor CCR5 antagonists, which provide a novel mechanism of action, are a recent addition to the armamentarium of antiretroviral agents. Antiretroviral are an important break-through in the treatment of HIV/AIDS. However, adverse reactions from these drugs can range from mild to life-threatening, and determining which agent is the cause is frequently difficult to discern. Fortunately, side effects can be monitored, treated and in many cases, prevented.