The physical contrast sensitivity of microwave imaging systems employing scattering-parameter measurements is defined. Methodologies are proposed for its evaluation through measurements and through simulations. This enables the estimation of the smallest detectable target permittivity contrast or size for the system under evaluation. The outcomes of the proposed simulation-based and measurement-based methods are compared for the case of a realistic tissue-imaging system. The agreement between the simulated and measured sensitivity estimation validates the proposed methods. The intention of the proposed methodology is to provide common means to quantify and compare the sensitivity performance of microwave systems used in tissue imaging as well as the antennas used as sensors. We emphasize that the proposed method targets the performance of the hardware and it is not concerned with the image-reconstruction algorithms.