Cell-to-cell communication is essential for multicellular organisms and the combined effects of multiple signals determine a cell’s response. There are many ways that the cells that make up our tissues communicate with one another in order to send signals from one place in our bodies to another. One way is where molecules such as hormones travel through the bloodstream over longer distances to reach target cells that are located far away from the sending cell. Certain hormones are sensed by receptors that reside on the surfaces of cells, such as G protein coupled receptors (GPCRs). GPCRs respond to many stimuli that regulate smell, sight, mood, pain, and cardiovascular and nervous systems. As a result, these receptors are the targets of many drug development efforts and therefore make up about 30-40% of targeted receptors in clinical drugs. Previously, it was believed that GPCRs could only be activated at the plasma membrane and those residing inside of the cell were dormant or silent. However, some GPCRs can be activated within the cell. The beta-1 and beta-2 adrenergic receptors (β1AR and β2AR, respectively) are GPCRs that regulate heart function and are activated by hormones released by the sympathetic system such as epinephrine and norepinephrine. β1AR and β2AR are located at the plasma membranes of cardiomyocytes but also have internal residences at organelles such as the Golgi apparatus for β1AR and endosomes for β2AR. It was recently found that the receptors that live at the Golgi and endosomes contribute to distinct signaling responses and provide different cellular outputs than cell surface receptors. This discovery is important because deciphering how the different receptor pools are regulated can aid in the development of appropriate drugs that target the correct receptor pool. Furthermore, β1AR and β2AR can couple to more than one G protein type, adding another layer of signaling dynamics that can occur in cardiovascular biology. The work detailed in chapter 2 provides a potential mechanism on how this dual coupling may be regulated. Chapter 3 focuses on deciphering the molecular determinants of β1AR Golgi retention. Chapter 4 sheds light on the distinct interactomes that arise when β1AR is activated at the plasma membrane versus the Golgi apparatus using proximity labeling, as was previously done for β2AR. Lastly, chapter 5 explores how G protein dual coupling may be manipulated by using drugs that bias β1AR to one G protein over another. This work reveals interesting pathways for βARs that reside in distinct compartments and furthers our knowledge of cardiovascular function, and it can also reveal properties of other receptors in the GPCR family that can signal internally.