This review highlights cave habitats, cave microbiomes and their potential for drug discovery. Such studies face many challenges, including access to remote and pristine caves, and sample collection and transport. Inappropriate physical and chemical growth conditions in the laboratory for the isolation and cultivation of cave microorganisms pose many complications including length of cultivation; some cave microorganisms can take weeks and even months to grow. Additionally, DNA extraction from cave environmental samples may be difficult due to the high concentration of various minerals that are natural DNA blocking agents. Once cave microorganisms are grown in the lab, other problems often arise, such as maintenance of pure culture, consistency of antimicrobial activity and fermentation conditions for antimicrobial production. In this review, we suggest that, although based on what has been done in the field, there is potential in using cave microorganisms to produce antimicrobial agents, one needs to be highly committed and prepared.