The paper summarizes twenty years of studies in crustal sensitive zones. Sensitive zones show prominent geophysical responses to stress and strain changes and high-amplitude and distant preseismic and postseismic effects. Four sensitive zones are known today in Turkmenistan, Uzbekistan, Armenia, and northeastern China, which occur at junctions of large crustal blocks. High-amplitude and distant responses are due to deformation and high strain sensitivity of geophysical parameters along block boundaries. Data from sensitive zones are used to investigate earthquake-related effects as controlled by crustal heterogeneity and nonlinearity. These effects act also outside sensitive zones and should be taken into account when interpreting precursor signals. The knowledge of sensitive zones has important implications for active deformation along block boundaries.