The convergence of biology, technology, and medicine has revolutionised healthcare, with microbial biotechnology at the forefront. While many microbes are often considered solely for their infectious properties, many are major producers of natural products, including antimicrobials. Now, not only sources of clinically relevant drugs, they are also being directly engineered for advanced applications such as targeted drug delivery, immune modulation, and precision therapeutics. Microorganisms are key sources of novel antimicrobials, immunomodulatory, and anticancer agents, which synthetic biology and genomics mining can exploit. Bioengineering and exploration of underused microbial taxa offer promising solutions to the problem of rising antimicrobial resistance. Microbes also play crucial roles in modern vaccine development, from live attenuated to recombinant antigen production. The human microbiome has emerged as an interesting player in health, driving innovations in diagnostics and therapies that include next-generation probiotics and microbiota transplants. Furthermore, synthetic biology further empowers the design of ‘smart’ microbes for in situ therapeutic functions like imaging, biosensing, and targeted treatment. While transformative, these innovations also raise critical ethical and regulatory concerns, including biosafety, ecological impact, data privacy, and equitable access. This chapter explores the multifaceted roles of microbes in medical biotechnology—spanning therapeutics, vaccines, microbiome-based interventions, and engineered systems—underscoring their importance in the evolution of sustainable, personalised healthcare.