Initiation and maintenance of antiseizure therapy can be relatively straightforward in most patients. Depending on epilepsy type, patients may be more or less likely to enter remission or a resolution of their epilepsy and the International League Against Epilepsy developed clinically guiding definitions in this regard. The mechanisms by which resolution or remission are achieved are poorly understood which complicates clinical decision making and risk estimate for future seizure relapse. The impetus for the maintenance of medical therapy in a seizure-free patient is also age-dependent. In children, one ought to consider the unknown effects of antiseizure medications on the developing brain while family planning, lifestyle, education, or employment are some of the issues that affect the decision making in adults. Patients who enter remission following surgical remediation of their epilepsy represent a distinct category and medication discontinuation is influenced by a number of factors. Another important consideration is comorbidities that often affect medication choices and maintenance. When formulating a management strategy, patient preferences together with careful evaluation and precise and accurate epilepsy diagnosis are key towards guiding medical or surgical management, prognostication for seizure freedom, relapse risk, options for medication discontinuation, and understanding risks and types of comorbidities.