Obesity became an epidemic public health problem and continuously increasing every year. For the longest time, the pathologic framework for obesity had been simple: caloric intake is greater than the energy output, which by far still true, however, the underlying reasons for increased energy intake and reduced energy expenditure remain largely unknown. Emerging data indicate that obesity can be oftentimes secondary to an underlying pathology, which can be due to genetics, inflammation, microbiome dysbiosis, metabolism, drugs and several other reasons. In this chapter, we described the pathology of obesity and underlying factors are linked or contributing in its progression.