Infectious disease remains one of the largest burdens on humankind. Even with modern medical and public health standards, infectious disease remained the No. 1 killer worldwide at the turn of the century. Often, the most costly disease burdens come from multiple infections at once, i.e., coinfection. Influenza, an annual infection often considered relatively harmless, can increase susceptibility to both deadly bacterial pneumonia and childhood ear infections. Major health threat HIV rarely kills a patient on its own, but instead allows for opportunistic infections and re-emergence of infections such as tuberculosis. What generates these unique relationships is not well understood; herein, we examine in detail three types of coinfection and the unique interactions between infectious agents as well as with the host in each setting. We also begin to address how we may aid further understanding of coinfection and what questions need to be addressed to help direct future treatments.