The epigenome, comprising DNA and histone modifications alongside intricate chromatin structures, has emerged as pivotal players in disease development. These factors offer promising opportunities for therapeutic interventions, expanding the avenues traditionally explored within genetic elements. Eukaryotic chromatin exhibits an impressive capacity for computation and information storage, fueled by the dynamic interplay of factors that modify the physicochemical states of chromatin. With its unique attributes, chromatin emerges as a compelling candidate for synthetic intervention and therapeutic reprogramming. In this review, we explore pioneering initiatives aimed at synthetically manipulating the epigenome, a relatively uncharted domain with transformative potential for both diagnostics and treatments.