Antiplatelet agents are used worldwide mainly for primary and secondary prevention of cardiovascular events on a long-term basis for mortality benefit. Gastrointestinal bleeding is a well-known adverse effect. Various factors are to be considered while choosing antiplatelet agents to prevent the risk of bleed and rebleed incidents. These range from deciding on the agent, timing of therapy, underlying indications, coadministration of proton pump inhibitor, etc. At the same time, one must weigh the risks of cardiovascular events secondary to the stoppage of antiplatelet therapy. With this review, we have tried to guide the clinician on decision-making regarding the care of patients on management of acute upper and lower gastrointestinal bleeding, stoppage, restarting of agents, and measures to prevent a recurrence. We have focused on aspirin and clopidogrel as they are among the most widely used antiplatelet agents.