Tissues exhibiting quasi-periodic structures can be modeled as a collection of diffuse scatterers and coherent scatterers. The mean scatterer spacing (MSS) of coherent and quasi-periodic components is directly related to tissue microstructure and has become an important quantitative ultrasound (QUS) parameter in the characterization of quasi-periodic tissues. In this paper, a review of the literature on the development of MSS as a QUS parameter was conducted. First, a unified theoretical background of MSS estimates was provided. Then, the application of MSS estimates was summarized with respect to liver, spleen, breast, bone, muscle, and other tissues. MSS estimation techniques were applied to (a) the diagnosis of hepatitis, liver fibrosis and cirrhosis, and lesions in tissues such as liver, breast, and spleen; (b) the differentiation between benign and malignant breast tumors, and the grading of breast cancer; (c) the detection of cancellous bone; and (d) the monitoring of the efficacy of treatments such as thermal ablation, with various levels of success. Future developments were also discussed in terms of real-time implementation of MSS estimates, local MSS estimation, relationship of MSS to other QUS parameters, combination of MSS with other QUS parameters, in vivo validation of MSS estimates, MSS parametric imaging, and three-dimensional ultrasound tissue characterization.