Viral and bacterial respiratory tract infections are a leading cause of morbidity and mortality worldwide, despite the development of vaccines and potent antibiotics. Frequently, viruses and bacteria can co-infect the same host, resulting in heightened pathology and severity of illness compared to single infections. Bacterial superinfections have been a significant cause of death during every influenza pandemic, including the 2009 H1N1 pandemic. This review will analyze the epidemiology and global impact of viral and bacterial co-infections of the respiratory tract, with an emphasis on bacterial infections following influenza. We will next examine the mechanisms by which viral infections enhance the acquisition and severity of bacterial infections. Finally, we will discuss current management strategies for diagnosing and treating patients with suspected or confirmed viral-bacterial infections of the respiratory tract. Further investigation into the interactions between viral and bacterial infections is necessary for developing new therapeutic approaches aimed at mitigating the severity of co-infections.