Follicular lymphoma (FL) is the most common indolent non-Hodgkin’s lymphoma in northern America. FL is an incurable disease with relapsing–remitting courses requiring serial intermittent treatments. Duration of remission will often become progressively shorter and most patients will die from refractory disease or transformation to aggressive lymphoma. Given the incurable nature of FL, current goals of treatment are focused on improving symptoms and survival by a variety of available treatment options, while considering potential adverse events. Although randomized controlled trials are universally perceived as the gold standard of clinical research, randomized controlled trials are not always practical and have several limitations. Therapeutic and diagnostic options of FLs are expanding faster than randomized controlled trials can test them, so employing comparative effectiveness research on other research designs are needed to efficiently improve global FL care. Implementing comparative effectiveness research with judicious use of appropriate research designs will hopefully fill current knowledge gaps and provide insights for FL managements.