Masonry structures, particularly historic buildings such as towers, churches, and palaces, represent a significant part of Europe’s architectural heritage. Due to aging materials and structural pathologies that have arisen over the years, many of these buildings have experienced deteriorated structural performance. In addition, these structures are often exposed to significant seismic hazard, which is an aggravating factor, especially considering that most of them were designed only to resist vertical loads or with primitive seismic design principles. As a result, the preventive conservation of historic masonry buildings is a critical priority, requiring effective diagnostic tools and strategies to promptly assess the in-service deterioration of these structures. In this work, the innovative concept of “smart masonry” for Structural Health Monitoring (SHM) of masonry structures is introduced, which relies on the use of self-sensitive construction materials to build distributed sensor networks integrated within the masonry load-bearing structures. Specifically, this innovative SHM approach proposes the use of a novel class of piezoresistive brick-like sensors, called smart bricks, to measure damage-induced changes in strain at key points of the structure, and of electrically conductive smart mortar layers to detect crack formation and propagation. It also includes the use of automated damage detection algorithms specifically developed to link field observations related to the building’s in-service condition, gathered by these sensitive materials, to its structural safety. The paper also reports the latest full-scale applications of the “smart masonry” approach, with a focus on the use of smart bricks to perform distributed strain monitoring and damage detection in masonry structures.