The synthesis of plant-wide control structures has resurfaced as the most important design problem in process control. In this paper we provide a comparative analysis of various approaches, with an emphasis on how well they address the inherent theoretical and practical issues associated with the design of such control systems. Starting with a formal statement of the problem, which corresponds to a multi-objective optimization problem, this paper argues that the central issue to be resolved is the translation of implicit operating objectives to sets of feedback-controlled variables. The principle of the Optimizing Feedback Control Structures is proposed as the formal medium for the identification of controlled variables. Furthermore, it is shown that the selection of the best sets of input (manipulated) and output (measured) variables for the formation of the controllers＇ structures is governed by classical control-theoretical aspects, such as; open-loop gains, model uncertainty, and nonminimum-phase process characteristics. Hierarchical viewing of a plant is proposed as an effective mechanism to contain the complexities of the problem by streamlining the (i) specification of control objectives at different time-scales, (ii) modeling needs and model uncertainties, (iii) selection of measured and manipulated variables, and (iv) formation of the control structures. (C) 2000 IFAC,