Polyadenosine diphosphate ribose (polyADPR) and polyADPR-polymerase (polyADPR-P) were discovered in our laboratory in 1966. Then it has been demonstrated that the enzyme and the polymer exist in all eukaryotic cells and catalyze a transfer of ADP-ribose moieties to proteins. Ever increasing evidence favours an involvement of the enzyme through protein ADP-ribosylation in DNA duplication, transcription and repair. Recently the existence of poly or oligo ADP-ribosyl transferases were demonstrated in mitochondria and cytoplasmic particles which carry messenger RNA (mRNP). The nuclear DNA dependent ADPR polymerase produces ADP-ribosylation of a great number of nuclear proteins, resulting in polynucleosome relaxation and modulation of several nuclear enzymes activity. The mRNP ADP-ribosyl transferase may be implicated in derepression of the repressed mRNA. Since 1968 enzymes producing monoADP-ribosylation were discovered in several bacterial toxins and since 1975 in animal tissues. Nicotinamide and its structural analogue: 3-aminobenzamide inhibits ADP-ribosylation and by thus causing inhibition of cell proliferation. Some effects of these inhibitors on cell proliferation are reported and the possible use in tumoral growth as an adjuvant of antimitotics is discussed. Thus ADP-ribosylation appears to be a basic multifunctional event with multiple target sites, some of which are of interest for antitumor therapy.