Here we compare label-free live-cell imaging versus fluorescence live-cell imaging. Although both techniques have become extremely important in the field of cell culture, there are certain issues to consider when using them. While label-free live-cell imaging is non-invasive, it is harder to visualize specific structures and proteins. Also, the preparation time and skills of the researcher need to be taken into consideration, as fluorescent live-cell imaging is more time-consuming, high in cost, and difficult to set up. In addition, because of its non-invasiveness, label-free live-cell imaging can be used with a higher temporal resolution without changing the culture conditions.