The variegated family of two-dimensional (2D) crystals has developed rapidly since the isolation of its forerunner: Graphene. Their planeconfined nature is typically associated with exceptional and peculiar electronic, optical, magnetic, and mechanical properties, heightening the interest of fundamental science and showing promise for applications. Methods for tuning their properties on demand have been pursued, among which the application of mechanical stresses, allowed by the incredible mechanical robustness and flexibility of these atomically thin materials. Great experimental and theoretical efforts have been focused on the development of straining protocols and on the evaluation of their impact on the peculiar properties of 2D crystals, revealing a novel, alluring physics. The relevance held by strain for 2D materials is introduced in Sec. I. Sections II and III present the multiplicity of methods developed to induce strain, highlighting the peculiarities, effectiveness, and drawbacks of each technique. Strain has largely widened the 2D material phase space in a quasi-seamless manner, leading to new and rich scenarios, which are discussed in Secs. IV-VI of this work. The effects of strain on the electronic, optical, vibrational, and mechanical properties of 2D crystals are discussed, as well as the possibility to exploit strain gradients for single-photon emission, non-linear optics, or valley/spintronics. Quantitative surveys of the relevant parameters governing these phenomena are provided. This review seeks to provide a comprehensive state-of-the-art overview of the straining methods and strain-induced effects, and to shed light on possible future paths. The aims and developments, the tools and strategies, and the achievements and challenges of this research field are widely presented and discussed.