Virtual sensors, or soft sensors, have greatly contributed to the evolution of the sensing systems in industry. The soft sensors are process models having three fundamental categories, namely white-box (WB), black-box (BB) and gray-box (GB) models. WB models are based on process knowledge while the BB models are developed using data collected from the process. The GB models integrate the WB and BB models for addressing the concerns, i.e., accuracy and intuitiveness, of industrial operators. In this work, various design aspects of the GB models are discussed followed by their application in the process industry. In addition, the changes in the data-driven part of the GB models in the context of enormous amount of process data collected in Industry 4.0 are elaborated.