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Brownfields (as abandoned and unused sites and buildings) are an integral part of urban consequences of human activities that can be transformed into a source that has not been used so far on both regional and national levels. As brownfields are typical by their set of negative externalities, reusing brownfields, either partially or fully, might be perceived as one of the aspects of sustainable development. The society-wide concerns for brownfield regeneration create pressure on owners of brownfields and public institutions to target their activities on solving the problems connected to their occurrence and to search for their new or alternative uses by abiding conditions of societal and environmental responsibility. The search for solutions concerning brownfield re-use might be based on plenty of theoretical recommendations and experiences from praxis. With a reference to the aim of this contribution, the systemic approach in brownfield regeneration will be introduced in the paper. Sub-systemic approaches will be also studied. These are grounded in mental models and the complexity theory, specifically in the presently most accentuated approach called the SMART approach. By means of these models, we are able to determine and define suitable regeneration processes for individual unused buildings or sites. The core of the systemic approach lies in analysis, modelling and description of cognitive processes and principles. They characterize the way of dealing with reality and are closely interconnected with the study of natural and anthropogenic systems. At the same time, the SMART approach is generally typical by using highly sophisticated analytical methods, approaches, ways of communication and techniques for designing the aims, processes and planning of brownfield regeneration. The SMART approach is significantly linked to the process of transfer of SMART solutions into material and non-material innovations. An analogy to the theoretical delimitation of approaches.