Investigating gene tissue specificity is an important step to understand life process and tissue functions. Despite the long history of research about housekeeping genes and tissue specific genes, their definition and detection methods are various. Housekeeping genes and tissue specific genes can be defined from the aspect of tissue expression number and expression variation across tissues, respectively. In general, housekeeping genes are usually defined as those expressed in most tissues with stable expression levels, while tissue specific or tissue selective genes are defined as those predominantly expressed in one tissue or a few tissues. High-throughput technology, such as microarray, RNA-seq and mass spectrometry have become the main methods to detect the tissue specificity of genes. By comparing the experimental results of some typical researches, we found there are significant differences between different methods in their coverage and sensitivity. In these methods, RNA-seq was the most sensitive, which can detect the most number of housekeeping genes, while mass spectrometry can only detect less tissue specific genes, and the results from different microarray experiments were various. Despite different definition and technology can lead to different housekeeping and tissue specific gene datasets, these datasets have very consistent functions and characters. Housekeeping genes usually implement fundamental functions of tissues or cells, while tissue specific genes perform most specific functions of tissues. Meanwhile, the tissue specificity of genes has close relations with diseases. Compared to other genes, housekeeping genes tend to become cancer genes, while tissue specific genes are more like to become drug targets.