Separating and identifying chemicals based on their masses and number of charges is an analytical technique known as mass spectrometry. Using mass spectrometry techniques to study large biomolecules has been a long-time dream in many areas of biology and medicine; however, classical molecule preparation methods proved unusable for biomolecules. Using heat was the traditional route for the evaporation of molecules, but evaporating the large biomolecules this way would cause them to lose their chemical structure and be destroyed. Electrospray ionization (ESI) and soft laser desorption (SLD) are two breakthrough methods that evaporate and ionize large biomolecules while retaining their chemical structure. These two methods were so impactful that they shared the 2002 Nobel Prize in chemistry. We employ both techniques in our mass spectrometry facility. We will discuss these techniques' similarities, differences, strengths, and weaknesses while providing real-world examples of large biomolecules we are actively investigating in the Department of Chemistry and Chemical Biology here at UNM. These examples illustrate that the future of these techniques will continue to enable scientific discoveries for years to come._