Infection stones are complex aggregates of crystals amalgamated in an organic matrix that are strictly associated with urinary tract infections. The management of patients who form infection stones is challenging owing to the complexity of the calculi and high recurrence rates. The formation of infection stones is a multifactorial process that can be driven by urine chemistry, the urine microenvironment, the presence of modulator substances in urine, associations with bacteria, and the development of biofilms. Despite decades of investigation, the mechanisms of infection stone formation are still poorly understood. A mechanistic understanding of the formation and growth of infection stones - including the role of organics in the stone matrix, microorganisms, and biofilms in stone formation and their effect on stone characteristics - and the medical implications of these insights might be crucial for the development of improved treatments. Tools and approaches used in various disciplines (for example, engineering, chemistry, mineralogy, and microbiology) can be applied to further understand the microorganism-mineral interactions that lead to infection stone formation. Thus, the use of integrated multidisciplinary approaches is imperative to improve the diagnosis, prevention, and treatment of infection stones.