Industrial plants are going to face a deep renewing process within the Industry 4.0 scenario. New paradigms of production lines are foreseen in the very near future, characterized by a strict collaboration between humans and robots and by a high degree of flexibility. Such envisaged improvements will require the smart use of proper sensors at very different levels. This paper investigates three different aspects of this industrial renewing process, based on three different ways of exploiting sensors, toward a new paradigm of a production line. The provided contributions, offering various types of innovation and integration, are relative to: (i) a virtual sensor approach for manual guidance, increasing the potentialities of a standard industrial manipulator, (ii) a smart manufacturing solution to assist the operator’s activity in manual assembly stations, through an original exploitation of multiple sensors, and (iii) the development of an advanced robotic architecture for a flexible production line, in which a team of autonomous mobile robots acts as a meta-sensor net supporting traditional automated guided vehicles. Accurate analyses of existing state-of-the-art solutions compared with the proposed ones are offered for the considered issues.