Two-dimensional (2D) crystals are attractive due to their intriguing structures and properties which are strongly dependent on the synthesis conditions. To achieve their superior properties, it is of critical importance to fully understand the growth processes and mechanisms for tailored design and controlled growth of 2D crystals. Due to the high spatiotemporal resolution and the capability to mimic the realistic growth conditions, in situ transmission electron microscopy (TEM) becomes an effective way to monitor the growth process in real-time at the atomic scale, which is expected to provide atomic-scale insights into the nucleation and growth of 2D crystals. Here we review the recent in situ TEM works on the formation of 2D crystals under electron irradiation, thermal excitation as well as voltage bias. The underlying mechanisms are also elucidated in detail, providing key insights into the nucleation and formation of 2D crystals.