Two-dimensional (2D) materials have tremendous potential to revolutionize the field of electronics and photonics. Unlocking such potential, however, is hampered by the presence of contaminants that usually impede the performance of 2D materials in devices. This perspective provides an overview of recent efforts to develop clean 2D materials and devices. It begins by discussing conventional and recently developed wet and dry transfer techniques and their effectiveness in maintaining material "cleanliness". Multi-scale methodologies for assessing the cleanliness of 2D material surfaces and interfaces are then reviewed. Finally, recent advances in passive and active cleaning strategies are presented, including the unique self-cleaning mechanism, thermal annealing, and mechanical treatment that rely on self-cleaning in essence. The crucial role of interface wetting in these methods is emphasized, and it is hoped that this understanding can inspire further extension and innovation of efficient transfer and cleaning of 2D materials for practical applications.