The immune system has a complicated job that involves being able to tell the difference between potentially harmful microbes and those that are helpful to humans. Correct immune responses are critical to the maintenance of health, yet sometimes can get out of control and be the cause of disease. Many of our insights into the ways that the immune system works have come recently, but the field of immunology can trace its roots back to the pioneering work of Dr. Edward Jenner and his efforts to vaccinate people against smallpox. This article will serve as the introduction to a multi-part series aimed at understanding the very complex and important topic of how the immune system is able to detect threats, mount appropriate responses, and yet not get out of control. This first article introduces the concept of harmful versus beneficial microbes, how vaccines have impacted health and our understanding of immunology, and the central role of T helper lymphocytes in directing appropriate immune responses.