Ibudilast (IBD) is a non‑selective (3, 4, 10, 11) phosphodiesterase (PDE) 
inhibitor, used mainly as a bronchodilator for the treatment of bronchial 
asthma. PDE play a central role in cellular function (e.g. differentiation, 
synaptic plasticity and inflammatory response) by metabolizing cyclic 
nucleotides. The results from preclinical and clinical studies indicate that IBD 
has a broader range of action through suppression of pro‑inflammatory cytokines 
(IL‑6, IL‑1β, TNF‑α), toll‑like receptor 4 blockade (TLR‑4), inhibition of a 
macrophage migration inhibitory factor (MIF), up‑regulation the 
anti‑inflammatory cytokine (IL‑10), and promotion of neurotrophic factors (GDNF, 
NGF, NT‑4). Recent data indicate that the efficacy of IBD appears to be 
independent from PDE inhibition activity and rather linked to glial activity 
attenuation. Additional advantages of IBD, such as crossing the blood-brain 
barrier, good tolerance and activity by oral administration, makes it a 
promising therapeutic candidate for treating neuroinflammatory conditions, where 
the currently available treatment remains unsatisfying due to poor tolerability 
and/or sub‑optimal efficacy. IBD has no direct receptor affinity with exemption 
of some undefined effect on adenosine receptors that makes the drug devoid of 
its receptors‑mediated adverse effects. Current article provides an overview of 
the pharmacology of IBD with a focus on preclinical and clinical data supporting 
its potential neuroprotective benefits for neurological conditions, including 
multiple sclerosis, neuropathic pain, medication overuse headache, stroke, 
opioid, alcohol and methamphetamine abuse.