Efforts to reveal the molecular, cellular, and circuit mechanisms of addiction have largely focused on neurons. Yet accumulating data regarding the ability of glial cells to impact synaptic function, circuit activity, and behavior demands that we explore how these nonneuronal cells contribute to substance use disorders and addiction. Important work has shown that glial cells, including microglia, exhibit changes in phenotype following exposure to drugs of abuse and that modification of glial responses can impact behaviors related to drug seeking and drug taking. While these are critical first steps to understanding how microglia can impact addiction, there are still substantial gaps in knowledge that need to be addressed. This chapter reviews some of the key studies that have shown how microglia are affected by and can contribute to addiction. It also discusses areas where more knowledge is urgently needed to reveal new therapeutic and preventative approaches.