Although outcomes for follicular lymphoma (FL) continue to improve, it remains incurable for the majority of patients. Through next generation sequencing (NGS) studies, we now recognize that the genomic landscape of FL is skewed toward highly recurrent mutations in genes that encode epigenetic regulators co-occurring with the pathognomonic t(14;18) translocation. Adopting these technologies to study longitudinal and spatially-derived lymphomas has provided unique insights into the tumoral heterogeneity, clonal evolution of the disease and supports the existence of a tumor-repopulating population, considered the Achilles' heel of this lymphoma. An in-depth understanding of the genomics and its contribution to the disease pathogenesis is identifying new biomarkers and therapeutic targets that can be translated into clinical practice and, in the not too distant future, enable us to start considering precision-based approaches to the management of FL.