This article summarises the current knowledge of the action of E2 and P4 in the human endometrium and the mammary gland. To understand both sides of the action of steroid hormones – in normal physiology and especially in pathology – it is important to understand the molecular intracellular events of E2 and P4 in tissue-type manner. The same hormones could have different or even opposite effects in different human tissues. Thus, attention should be paid to the possible side effects of steroid hormones or their analogues before their use in clinical practice. Questions still remain about aberrations of the endometrium leading to implantation failure, endometriosis and other dysregulations. Even though studies of breast cancer development continuously unravel new information about the mechanisms leading from normal to malignant tissue proliferation, breast cancer is still the most fatal cancer type among women. As the number of couples seeking for aid to achieve fertility is constantly increasing a better understanding of the factors necessitating successful treatment as well as of possible side effects is crucial. The authors would like to emphasise the importance of next generation sequencing (NGS) technologies which are believed to be a key in understanding hormone dependent action in the whole organism. Analysis of data from NGS is still complicated and requires excellent computational skills but hopefully the data collected today will become the knowledge of tomorrow.