Widely used medical imaging systems in clinics currently rely on X-rays, magnetic resonance imaging, ultrasound, computed tomography, and positron emission tomography. The aforementioned technologies provide clinical data with a variety of resolution, implementation cost, and use complexity, where some of them rely on ionizing radiation. Microwave sensing and imaging (MSI) is an alternative method based on nonionizing electromagnetic (EM) signals operating over the frequency range covering hundreds of megahertz to tens of gigahertz. The advantages of using EM signals are low health risk, low cost implementation, low operational cost, ease of use, and user friendliness. Advancements made in microelectronics, material science, and embedded systems make it possible for miniaturization and integration into portable, handheld, mobile devices with networking capability. MSI has been used for tumor detection, blood clot/stroke detection, heart imaging, bone imaging, cancer detection, and localization of in-body RF sources. The fundamental notion of MSI is that it exploits the tissue-dependent dielectric contrast to reconstruct signals and images using radar-based or tomographic imaging techniques. This paper presents a comprehensive overview of the active MSI for various medical applications, for which the motivation, challenges, possible solutions, and future directions are discussed.