Biosynthesized small molecules known as specialized metabolites often have valuable applications in fields such as medicine and agriculture. Consequently, there is always a demand for novel specialized metabolites and an understanding of their bioactivity. Methylotrophs are an underexplored metabolic group of bacteria that have several growth features that make them enticing in terms of specialized metabolite discovery, characterization, and production from cheap feedstocks such as methanol and methane gas. This chapter will examine the predicted biosynthetic potential of these organisms and review some of the specialized metabolites they produce that have been characterized so far.