Effective analytical techniques need to be developed to characterize the products of lignin degradation experiments to be able to generate renewable products from lignin. Mass spectrometry is an valuable analytical approach for lignin characterizaion, but it is hindered by lignin’s poor ionization efficiency, especially in the positive ion mode. In this work, we attempt to improve lignin’s ionization by utilizing electrospray and laser desorption mass spectrometry coupled with the addition of cations and chemical derivatives. We confronted the ionization problem from both a top-down and bottom-up analytical approach by analyzing synthesized monomers, dimers, and polymers along with natural lignin extracts from switchgrass. We also utilized tandem mass spectrometry to sequence lignin dimers and determine their bonding motifs from their fragmentation patterns. We believe that resolving the ionization issues with lignin will open the door for easier and more efficient lignin break-down techniques and ultimately more accessible renewable products from lignin.