Defining what is meant by "mental illness" has three dimensions: (i) the ontological dimension, which attempts to answer the question of what is a mental illness in itself, (ii) the scientific dimension, which attempts to identify its causes, and (iii) the practical dimension, which will seek a treatment. This article uses depression to examine how various conceptual alternatives in contemporary literature attempted to tackle the problem of what is a mental illness. After evaluating the scope of their proposals in the three dimensions mentioned above, it is concluded that the biomedical model could become a good candidate for developing a useful framework for understanding, having a scientific explanation and treating depression.