A TLR antagonist compound having the structure 5'-N m - N 3 N 2 N 1 CGN 1 N 2 N 3 - N m -3': wherein: CG is an oligonucleotide motif and C is cytosine or a pyrimidine nucleotide derivative, wherein the pyrimidine nucleotide derivative is selected from the group consisting of 5-hydroxycytosine, 5-hydroxymethylcytosine, N 4 -alkylcytosine, N 4 -ethylcytosine, araC, 5-OH-dC, N 3 -Me-dC, and 4-thiouracil; G is guanosine or a purine nucleotide derivative, wherein the purine nucleotide derivative is selected from the group consisting of 7-deaza-G, 7-deaza-dG, ara-G, 6-thio-G, Inosine, Iso-G, loxoribine, TOG(7-thio-8-oxo)-G, 8-bromo-G, 8-hydroxy-G, 5-aminoformycin B, Oxoformycin, 7-methyl-G, 9-p-chlorophenyl-8-aza-G, 9-phenyl-G, 9-hexyl-guanine, 7-deaza-9-benzyl-G, 6-Chloro-7-deazaguanine, 6-methoxy-7-deazaguanine, 8-Aza-7-deaza-G, 2-(Dimethylamino)guanosine, 7-ethyl-6-thioguanosine, 8-Benzyloxyguanosine, 9-Deazaguanosine, 1-(B-D-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine, and 1-{2'-deoxy-β-D-ribofuranosyl}-2-oxo-7-deaza-8-methyl-purine; N1-N3, at each occurrence, is independently a nucleotide, nucleotide derivative which is a purine or pyrimidine nucleotide having a base that is not guanine, cytosine, adenine, thymine or uracil and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an oligonucleotide or non-nucleotide linkage that can link or be linked to the oligonucleotides other than through a phosphorous-containing linkage; Nm, at each occurrence, is independently a nucleotide, nucleotide derivative which is a purine or pyrimidine nucleotide having a base that is not guanine, cytosine, adenine, thymine or uracil and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an oligonucleotide or non-nucleotide linkage that can link or be linked to the oligonucleotides other than through a phosphorous-containing linkage; provided that at least one N1 to N3 is a nucleotide derivative or non-nucleotide linkage; and further provided that the compound contains less than 4 consecutive guanosine nucleotides; wherein the oligonucleotide motif would be immune stimulatory but for the nucleotide derivative or non-nucleotide linkage; wherein m is a number from 0 to about 30; and wherein the TLR antagonist compound is not an antisense oligonucleotide; for use in therapeutically treating or preventing a disease mediated by a TLR in a vertebrate, wherein the disease is cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen. CG is an oligonucleotide motif and C is cytosine or a pyrimidine nucleotide derivative, wherein the pyrimidine nucleotide derivative is selected from the group consisting of 5-hydroxycytosine, 5-hydroxymethylcytosine, N 4 -alkylcytosine, N 4 -ethylcytosine, araC, 5-OH-dC, N 3 -Me-dC, and 4-thiouracil; G is guanosine or a purine nucleotide derivative, wherein the purine nucleotide derivative is selected from the group consisting of 7-deaza-G, 7-deaza-dG, ara-G, 6-thio-G, Inosine, Iso-G, loxoribine, TOG(7-thio-8-oxo)-G, 8-bromo-G, 8-hydroxy-G, 5-aminoformycin B, Oxoformycin, 7-methyl-G, 9-p-chlorophenyl-8-aza-G, 9-phenyl-G, 9-hexyl-guanine, 7-deaza-9-benzyl-G, 6-Chloro-7-deazaguanine, 6-methoxy-7-deazaguanine, 8-Aza-7-deaza-G, 2-(Dimethylamino)guanosine, 7-ethyl-6-thioguanosine, 8-Benzyloxyguanosine, 9-Deazaguanosine, 1-(B-D-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine, and 1-{2'-deoxy-β-D-ribofuranosyl}-2-oxo-7-deaza-8-methyl-purine; N1-N3, at each occurrence, is independently a nucleotide, nucleotide derivative which is a purine or pyrimidine nucleotide having a base that is not guanine, cytosine, adenine, thymine or uracil and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an oligonucleotide or non-nucleotide linkage that can link or be linked to the oligonucleotides other than through a phosphorous-containing linkage; Nm, at each occurrence, is independently a nucleotide, nucleotide derivative which is a purine or pyrimidine nucleotide having a base that is not guanine, cytosine, adenine, thymine or uracil and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an oligonucleotide or non-nucleotide linkage that can link or be linked to the oligonucleotides other than through a phosphorous-containing linkage; provided that at least one N1 to N3 is a nucleotide derivative or non-nucleotide linkage; and further provided that the compound contains less than 4 consecutive guanosine nucleotides; wherein the oligonucleotide motif would be immune stimulatory but for the nucleotide derivative or non-nucleotide linkage; wherein m is a number from 0 to about 30; and wherein the TLR antagonist compound is not an antisense oligonucleotide; for use in therapeutically treating or preventing a disease mediated by a TLR in a vertebrate, wherein the disease is cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.