Animals, including humans, have stable relationships with communities of microorganisms collectively referred to as the microbiota. These communities profoundly influence the biology of their hosts, impacting host features such as immune function, metabolism, and even so-called “higher” traits such as cognition and social behavior. Due to the wide range of microbiota-associated effects on host biology, understanding host-microbe relationships is not only important for understanding the normal physiology of the host, but may also allow us to use the microbiota to intentionally shape host health. We focus on several areas of host-microbe symbiosis, ranging from the fundamental features that govern these relationships to the translational prospects of using the microbiota to improve human health. This includes roles of intestinal bacteria in shaping host lipid and cholesterol metabolism, interactions between the microbiota and neurotransmitters, and the biophysical drivers of microbial colonization. We employ diverse techniques from molecular biology, biochemistry, and a variety of -omics platforms to explore our interactions with our microbial partners.