Microbes (bacteria, archaea, fungi, and viruses) are the most diverse and numerically abundant entities on our planet. However, we know surprisingly little regarding the vast microbial universe within and beyond us. The past two decades of sequencing-enabled research have revealed remarkable insights regarding the diversity and functional attributes of microbial communities, yet we lack comparative insights regarding African microbiomes. This talk will explore the importance of microbiomes in maintaining human health, as well as the challenges of studying these invisible organisms. I will highlight the unique potential of Africa’s rich biodiversity for “unlocking the secrets of microbiomes” and understanding their roles in shaping our world. I will also discuss the urgent need for increased investment in microbiome research and technology development in Africa, to ensure that the continent remains at the forefront of scientific discovery in this rapidly evolving field.