This paper is devoted to wall painting in the Middle Ages (ca. late fifth to early fifteenth centuries), with a focus on twelfth to fifteenth century Italy. It is conceived as a critical conflation of diverse methodologies, approaches and research tools, with the aim of investigating the topic from different and complementary perspectives. Historical textual sources provide the interpretive framework for the examination, which is conducted on specific, yet interrelated aspects. Special attention is paid to technical features, including the methods and materials used to produce wall paintings. Data from scientific investigations are incorporated into the discussion with the purpose of elucidating theoretical conceptualizations with material pieces of evidence. A number of selected case studies is presented within the text in order to keep the focus of analysis on the materiality of the paintings, hence avoiding the formulation of abstract concepts in favour of more pragmatic approaches.