There is increasing evidence suggesting that stoichiometric imbalances in macromolecular complexes and in signaling/transcriptional networks are a source of dosage-dependent phenotypes. Such alterations can result from total or partial aneuploidy, gene copy number variants or regulatory alterations. Thus, some gene balance is required to ensure a normal function. This balance also dictates which genes are preferentially over- or underretained after single gene, segmental or whole genome duplications. Here, we review the mechanisms leading to dosage effects and compensation at the transcriptional and translational levels. Moreover, we propose that the involvement of a protein in a complex can affect its stability: formation of complexes might mask degradation signals in the monomers leading to their preferential degradation when in excess, alleviating dosage imbalances.