Wood has been widely used by humans for millennia as a construction material and can be easily found in everyday life, anywhere around the world. Since wood is a natural, sustainable, and organic composite material, it can be affected by several wood-deteriorating agents under suitable climate exposure conditions, which may threaten the long-term performance of timber structures in their service life. In that context, this chapter covers the background, guidelines, and current research that can help engineers and architects when designing timber structures. It provides extended knowledge about different wood-deteriorating agents, the natural durability of wood, and the use class concept. Based on this, durability models can be established, taking into account the potential presence over time of wood deterioration agents and allowing design for improved service life. Preventive measures and protection systems can be defined from the beginning, whereas on-site monitoring and maintenance of timber structures should be continuously performed.