Perpetuation of immune-deficiency throughout tumour development is, to a great degree, the result of impairment of DC function by products secreted by tumours. They include cytokines, non-tumour specific molecules (gangliosides, prostanoids, nitric oxide, etc) and tumour (specific) antigens (MUC-1, PSA, Her-2 neu). They may engender a distortion of DC development, block DC maturation, induce DC apoptosis or interfere with antigen presentation. Identifying those molecules and their interaction with DC will accelerate the development of more efficient immunotherapies. In this chapter we review the current literature on these interactions and highlight the possible avenues of minimisation of their deleterious effects.